It is proposed to study the effects of the fluoride salts (NaF and Na2PO3F) on cAMP and glucose metabolism. In one case we plan to administer fluoride by injection (acute) or in the diet (chronic). The acute studies will be aimed at determining the dose and time course of fluoride in inducing changes in tissue (heart, liver, kidney, epididymal fat tissue, submaxillary) and bone (tibia) cAMP levels. Also, we plan to examine if fluoride alters glucose and glycogen metabolism in the liver by assaying for liver glucose metabolite concentrations and attempt to determine the mechanism of action of fluoride. The chronic studies will be aimed at determining the effects of fluoridated water (1 ppm) or dietary fluoride (20 ppm) on the cAMP levels in tissue named above. Although we have shown that many of these tissues have an elevated cAMP level after 2-4 weeks on fluoride, it is not known if the elevation of cAMP persists for many weeks or months. The chronic experiments will be conducted for up to 16-20 weeks at which time the above-named tissues will be examined for cAMP. Also, it is proposed to examine the effect of chronic fluoride administration on glucose metabolism. It has been shown that after 2-4 weeks of dietary fluoride that there is an increase in some of the liver glycolytic intermediates such as 2-phosphoglycerate, 3-phosphoglycerate, and phosphoenolpyruvate. However, it is not known what effect fluoride has on liver glucose metabolism after 16-20 weeks. Thus it is proposed to examine the glycolytic intermediates and enzyme activities after 16-20 weeks on a fluoride diet. The second approach will be at the level of isolated cells. Research at present has shown that fluoride salts increase hepatocyte cAMP levels and decrease enolase and pyruvate kinase activities. It is proposed to expand these studies to examine the effect of fluoride salts on all the glycolytic enzyme activities, as well as those enzymes responsible for the synthesis and breakdown of glycogen. Also, we plan to examine the effect of NaF on the production of cAMP in isolated parotid cells.